Prader-Willi syndrome (PWS) is a genetic imprinting disorder in which at least seven genes on chromosome 15 are missing or wrongly expressed. PWS is characterized by diminished fetal activity, obesity, muscular hypotonia, mental retardation, short stature, hypogonadotropic hypogonadism, and small hands and feet. The frequency of PWS at about 1 in 25,000 and probably the most common syndromal cause of human obesity. The disease is caused by absence of the paternally derived PWS/AS region of chromosome 15 by one of several genetic mechanisms, including uniparental disomy, imprinting mutations, chromosome translocations, and gene deletions. The genes responsible for Prader-Willi syndrome are expressed only on the paternal chromosome. The risk to the sibling of an affected child of having PWS depends upon the genetic mechanism which caused the disorder. The risk to siblings is under 1% if the affected child has a gene deletion or uniparental disomy, up to 50% if the affected child has a mutation of the imprinting control center, and up to 25% if a parental chromosomal translocation is present.
Angelman syndrome (AS) is a neurological disorder in which severe learning difficulties are associated with a characteristic facial appearance and behaviour (symptoms include feeding problems, delay in sitting and walking, absent speech, poor attention span and hyperactivity, severe learning disabilities, Epilepsy, abnormal EEG, tremors, affectionate nature, frequent laughter, below average head size, characteristic facial features, Scoliosis) and others symptoms. Angelman syndrome is caused by the loss of the normal maternal allele function of a region on chromosome 15, most commonly by a large deletion of a segment of that chromosome. Other causes include uniparental disomy, translocation, or single gene mutations in that region (e.g. in Ube3a). A healthy person receives two copies of chromosome 15, one from mother, the other from father. However, in the region of the chromosome that is critical for Angelman syndrome, the maternal and paternal alleles express certain genes very differently. This is due to sex-related epigenetic imprinting (manifested by allele-specific DNA methylation). If the maternal contribution is lost, the result is Angelman syndrome. (When the paternal contribution is lost, by similar mechanisms, the result is Prader-Willi syndrome.) The most common genetic defect leading to Angelman syndrome is an ~ 4 Mb maternal deletion in chromosomal region 15q11-13 causing an absence of Ube3a expression in the maternally imprinted brain regions.
